Osteoporosis is a disease in which bones become fragile and more likely to fracture. Usually the bone loses density, which measures the amount of calcium and minerals in the bone. Osteoporosis is the most common type of bone disease. About half of all women over the age of 50 will have a fracture of the hip, wrist, or vertebra (bone of the spine) during their lifetime. Bone is living tissue. Existing bone is constantly being replaced by new bone. Osteoporosis occurs when the body fails to form enough new bone, when too much existing bone is reabsorbed by the body, or both. Calcium is one of the important minerals needed for bones to form. If you do not get enough calcium and vitamin D, or your body does not absorb enough calcium from your diet, your bones may become brittle and more likely to fracture. A drop in estrogen in women at the time of menopause and a drop in testosterone in men is a leading cause of bone loss.
Fractures caused by osteoporosis constitute a major health concern and result in a huge economic burden on health care systems. The lifetime risk of any osteoporotic fracture is high in the western world (around 50% for women and 20% for men) and fractures are associated with significant mortality and morbidity. Cortical bone constitutes approximately 80% of the bone in the body and several studies have shown that cortical bone is the major determinant of bone strength and thereby fracture susceptibility. Bone loss after the age of 65 is mainly due to loss in cortical bone and not trabecular bone (Lancet, 2010, May 15; 375(9727): 1729-36).
The skeleton is remodeled by bone forming osteoblasts (OBs) and bone resorbing osteoclasts (OCLs). Macrophage colony stimulating factor (M-CSF) increases proliferation and survival of OCLs precursor cells as well as up-regulates expression of receptor activator of nuclear factor-KB (RANK) in OCL. This allows RANK ligand (RANKL) to bind and start the signalling cascade that leads to OCL formation. The effect of RANKL can be inhibited by Osteoprotegerin (OPG), which is a decoy receptor for RANKL.
The association between inflammation and bone loss is well established and in auto-immune diseases osteoclastic bone resorption is driven by inflammatory cytokines produced by activated T-cells. In addition, several studies demonstrate that low-grade systemic inflammation, indicated by moderately elevated serum levels of high sensitivity C-reactive protein (hsCRP), associate with low BMD, elevated bone resorption and increased fracture risk. The estrogen deficiency that occurs after menopause results in increased formation and prolonged survival of osteoclasts. This is suggested to be due to a number of factors including loss of the immunosuppressive effects of estrogen, resulting in increased production of cytokines promoting osteoclastogenesis, and direct effects of estrogen on OCLs. In line with these data, blockade of the inflammatory cytokines TNFα and IL-1 leads to a decrease in bone resorption markers in early postmenopausal women.
In recent years, the importance of the gut microbiota (GM) for both health and disease has been intensively studied. The GM consists of trillions of bacteria which collectively contain 150-fold more genes than our human genome. It is acquired at birth and, although a distinct entity, it has clearly coevolved with the human genome and can be considered a multicellular organ that communicates with and affects its host in numerous ways. The composition of the GM is modulated by a number of environmental factors such as diet and antibiotic treatments. Molecules produced by the gut bacteria can be both beneficial and harmful and are known to affect endocrine cells in the gut, the enteric nervous system, gut permeability and the immune system. Perturbed microbial composition has been postulated to be involved in a range of inflammatory conditions, within and outside the gut including Crohn's disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, diabetes, food allergies, eczema and asthma as well as obesity and the metabolic syndrome.
Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and are believed to alter the composition of the gut microbiota. The suggested underlying mechanisms are manifold including increased solubility and absorption of minerals, enhanced barrier function and modulation of the immune system.
In Gilman et al, The effect of Probiotic Bacteria on Transepithelial Calcium Transport and Calcium uptake in Human Intestinal-like Caco-2 cells, Curr. Issues Intestinal Microbial. 7: 1-6, a strain of Lactobacillus salivarius (UCC 118) and a strain of Bifidobacterium infantis (UCC 35624) was tested on calcium uptake and transepithelial calcium transport in human intestinal-like Caco-2 cells in culture. Said strains had no effect on transepithelial calcium transport in fully differentiated 16-d old Caco-2 cells. Calcium uptake into the Caco-2 cell monolayers after 24 h was significantly higher in the cells exposed to Lactobacillus salivarius. 
WO99/02170 describes the use of lactobacilli in the preparation of non-fermented enteral compositions for facilitating or increasing the absorption of minerals from the diet such as calcium, zinc, iron and magnesium. The experiments performed therein, in supporting said claimed absorption, are an in vitro model of calcium transportation using Caco-2 intestinal lines (a carcinogenic cell line).
KR101279852 discloses compositions for prevention or treatment of osteoporosis containing calcium and magnesium in addition to specific lactic acid bacterial strains such as Streptococcus thermophilus with deposition number KCTC11870BP, Lactobacillus rhamnosus with deposition number KCTC 11868BP, and Lactobacillus paracasei with deposition number KCTC11866BP.
There is still a need within the art to find effective preventive and therapeutic methods against osteoporosis in humans.